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Purpose: The impact of ingesting carbohydrates alone or combined with proteins to support exercise immune adaptation in endurance athletes is scarcely investigated. The present study compares the effect of ingesting a combined protein–carbohydrate supplement vs. a carbohydrate-only supplement post-workout on immune inflammation markers following a 10 week periodized endurance training program in well-trained athletes. Methods: Twenty-five men completed the study after being randomly assigned to one of the following intervention groups: combined protein–carbohydrate (PRO-CHO n = 12, 31 ± 9 years, V ˙ O2peak 61.0 ± 5.6 ml.kg−1.min−1) or non-protein isoenergetic carbohydrate (CHO, n = 13, 33 ± 8 years, V ˙ O2peak 60.6 ± 6.9 ml.kg−1.min−1). Treatment consisted of ingesting 24 g of assigned supplement, mixed with 250 ml of orange juice, once a day for 10 weeks immediately post-workout (or before breakfast on non-training days). Measurements were conducted pre- and post-intervention on total leukocytes, leukocyte subsets (i.e., neutrophils, eosinophils, basophils, monocytes, and lymphocytes), and platelets. The inflammatory status was assessed by the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and the systemic-immune inflammation index (SII). Results: Post-intervention, significant increases were observed for CHO group only for the three inflammatory markers: NLR (p = 0.050, d = 0.58), PLR (p = 0.041, d = 0.60), and SII (p = 0.004, d = 0.81) but not for PRO-CHO (p > 0.05). Conclusion: Ingesting a post-workout protein–carbohydrate combined beverage promoted a more favourable immune status than carbohydrate-only ingestion by attenuating cellular inflammation over a 10 week training period in endurance male athletes. Trial Registration: The study was registered in ClinicalTrials.gov with the following ID: NCT02954367. The study was registered by 3 November 2016. [ABSTRACT FROM AUTHOR]